Chloroquine

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Chloroquine
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adeel Jamil, M.D. [2]

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Black Box Warning

WARNING
See full prescribing information for complete Boxed Warning.
* For Malaria and Extraintestinal Amebiasis

Overview

Chloroquine is a aminoquinoline antimalarial that is FDA approved for the treatment of for the suppressive treatment and for acute attacks of malaria due to P. vivax, P. malariae, P. ovale, and susceptible strains of P. falciparum. The drug is also indicated for the treatment of extraintestinal amebiasis.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include cardiovascular, dermatological, immunological, neurological and ophthalmological (see Adverse Reactions section).

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • Chloroquine phosphate tablets does not prevent relapses in patients with vivax or malariae malaria because it is not effective against exoerythrocytic forms of the parasite, nor will it prevent vivax or malariae infection when administered as a prophylactic. It is highly effective as a suppressive agent in patients with vivax or malariae malaria, in terminating acute attacks, and significantly lengthening the interval between treatment and relapse. In patients with falciparum malaria it abolishes the acute attack and effects complete cure of the infection, unless due to a resistant strain of P. falciparum.
Dosing Information
  • The dosage of chloroquine phosphate is often expressed or calculated as the base. Each 250 mg tablet of chloroquine phosphate is equivalent to 150 mg base. In infants and children the dosage is preferably calculated on the body weight.
  • Malaria:
  • Suppression— Adult Dose: 500 mg (= 300 mg base) on exactly the same day of each week.
  • If circumstances permit, suppressive therapy should begin two weeks prior to exposure. However, failing this in adults, an initial double (loading) dose of 1 g (= 400 mg base), or in children 10 mg base/kg may be taken in two divided doses, six hours apart. The suppressive therapy should be continued for eight weeks after leaving the endemic area.
  • For Treatment of Acute Attack:
  • An initial dose of 1 g (= 400 mg base) followed by an additional 500 mg (= 300 mg base) after six to eight hours and a single dose of 500 mg (= 300 mg base) on each of two consecutive days. This represents a total dose of 2.5 g chloroquine phosphate or 1.5 g base in three days.
  • The dosage for adults of low body weight and for infants and children should be determined as follows:
    • First dose: 10 mg base per kg (but not exceeding a single dose of 400 mg base).
    • Second dose: (6 hours after first dose) 5 mg base per kg (but not exceeding a single dose of 300 mg base).
    • Third dose: (24 hours after first dose) 5 mg base per kg.
    • Fourth dose: (36 hours after first dose) 5 mg base per kg.
  • Extraintestinal Amebiasis:
  • Adults:1 g (400 mg base) daily for two days, followed by 500 mg (300 mg base) daily for at least two to three weeks. Treatment is usually combined with an effective intestinal amebicide.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Chloroquine in adult patients.

Non–Guideline-Supported Use

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Dosing Information
  • The dosage of chloroquine phosphate is often expressed or calculated as the base. Each 250 mg tablet of chloroquine phosphate is equivalent to 150 mg base. In infants and children the dosage is preferably calculated on the body weight.
  • The weekly suppressive dosage is 5 mg calculated as base, per kg of body weight, but should not exceed the adult dose regardless of weight.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Chloroquine in pediatric patients.

Non–Guideline-Supported Use

Contraindications

  • Use of this drug is contraindicated in the presence of retinal or visual field changes either attributable to 4-aminoquinoline compounds or to any other etiology, and in patients with known hypersensitivity to 4-aminoquinoline compounds. However, in the treatment of acute attacks of malaria caused by susceptible strains of plasmodia, the physician may elect to use this drug after carefully weighing the possible benefits and risks to the patient.

Warnings

WARNING
See full prescribing information for complete Boxed Warning.
* For Malaria and Extraintestinal Amebiasis
  • It has been found that certain strains of P. falciparum have become resistant to 4- aminoquinoline compounds (including chloroquine and hydroxychloroquine). Chloroquine resistance is widespread and, at present, is particularly prominent in various parts of the world including sub-Saharan Africa, Southeast Asia, the Indian subcontinent, and over large portions of South America, including the Amazon basin1.
  • Before using chloroquine for prophylaxis, it should be ascertained whether chloroquine is appropriate for use in the region to be visited by the traveler. Chloroquine should not be used for treatment of P.falciparum infections acquired in areas of chloroquine resistance or malaria occurring in patients where chloroquine prophylaxis has failed.
  • If there is any indication (past or present) of abnormality in the visual acuity, visual field, or retinal macular areas (such as pigmentary changes, loss of foveal reflex), or any visual symptoms (such as light flashes and streaks) which are not fully explainable by difficulties of accommodation or corneal opacities, the drug should be discontinued immediately and the patient closely observed for possible progression. Retinal changes (and visual disturbances) may progress even after cessation of therapy.
  • Acute extrapyramidal disorders may occur with chloroquine. These adverse reactions usually resolve after treatment discontinuation and/or symptomatic treatment.
  • All patients on long-term therapy with this preparation should be questioned and examined periodically, including testing knee and ankle reflexes, to detect any evidence of muscular weakness. If weakness occurs, discontinue the drug.
  • A number of fatalities have been reported following the accidental ingestion of chloroquine, sometimes in relatively small doses (0.75 g or 1 g chloroquine phosphate in one 3-year-old child). Patients should be strongly warned to keep this drug out of the reach of children because they are especially sensitive to the 4-aminoquinoline compounds.
  • Use of chloroquine phosphate in patients with psoriasis may precipitate a severe attack of psoriasis. When used in patients with porphyria the condition may be exacerbated. The drug should not be used in these conditions unless in the judgment of the physician the benefit to the patient outweighs the potential risks.
  • Usage in Pregnancy: Radioactively tagged chloroquine administered intravenously to pregnant pigmented CBA mice passed rapidly across the placenta and accumulated selectively in the melanin structures of the fetal eyes. It was retained in the ocular tissues for five months after the drug had been eliminated from the rest of the body. There are no adequate and well-controlled studies evaluating the safety and efficacy of chloroquine in pregnant women. Usage of chloroquine during pregnancy should be avoided except in the suppression or treatment of malaria when in the judgment of the physician the benefit outweighs the potential risk to the fetus.
Precautions
  • Hematological Effects/Laboratory Tests
  • Complete blood cell counts should be made periodically if patients are given prolonged therapy. If any severe blood disorder appears which is not attributable to the disease under treatment, discontinuance of the drug should be considered.
  • Auditory Effects
  • In patients with preexisting auditory damage, chloroquine should be administered with caution. In case of any defects in hearing, chloroquine should be immediately discontinued, and the patient closely observed.
  • Hepatic Effects
  • Central Nervous System Effects
  • Patients with a history of epilepsy should be advised about the risk of chloroquine provoking seizures.

Adverse Reactions

Clinical Trials Experience

Special Senses:Ocular:=

Auditory:
Musculoskeletal System:
Gastrointestinal system:
Skin and appendages:
Hematologic system:
Nervous system:
Cardiac system:

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Chloroquine phosphate in the drug label.

Drug Interactions

Antacids and kaolin:=

  • Antacids and kaolin can reduce absorption of chloroquine; an interval of at least 4 hours between intake of these agents and chloroquine should be observed.
Cimetidine:
  • Cimetidine can inhibit the metabolism of chloroquine, increasing its plasma level. Concomitant use of cimetidine should be avoided.
Ampicillin:
  • In a study of healthy volunteers, chloroquine significantly reduced the bioavailability of ampicillin. An interval of at least two hours between intake of this agent and chloroquine should be observed.
Cyclosporine:
  • After introduction of chloroquine (oral form), a sudden increase in serum cyclosporine level has been reported. Therefore, close monitoring of serum cyclosporine level is recommended and, if necessary, chloroquine should be discontinued.
Mefloquine:

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • Radioactively tagged chloroquine administered intravenously to pregnant pigmented CBA mice passed rapidly across the placenta and accumulated selectively in the melanin structures of the fetal eyes. It was retained in the ocular tissues for five months after the drug had been eliminated from the rest of the body. There are no adequate and well-controlled studies evaluating the safety and efficacy of chloroquine in pregnant women. Usage of chloroquine during pregnancy should be avoided except in the suppression or treatment of malaria when in the judgment of the physician the benefit outweighs the potential risk to the fetus.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Chloroquine phosphate in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Chloroquine phosphate during labor and delivery.

Nursing Mothers

  • Because of the potential for serious adverse reactions in nursing infants from chloroquine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the potential clinical benefit of the drug to the mother.
  • The excretion of chloroquine and the major metabolite, desethylchloroquine, in breast milk was investigated in eleven lactating mothers following a single oral dose of chloroquine (400 mg base). The maximum daily dose of the drug that the infant can receive from breastfeeding was about 0.7% of the maternal start dose of the drug in malaria chemotherapy. Separate chemoprophylaxis for the infant is required.

Pediatric Use

  • A number of fatalities have been reported following the accidental ingestion of chloroquine, sometimes in relatively small doses (0.75 g or 1 g chloroquine phosphate in one 3-year-old child). Patients should be strongly warned to keep this drug out of the reach of children because they are especially sensitive to the 4-aminoquinoline compounds.

Geriatic Use

  • Clinical studies of chloroquine phosphate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.

Gender

There is no FDA guidance on the use of Chloroquine phosphate with respect to specific gender populations.

Race

There is no FDA guidance on the use of Chloroquine phosphate with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Chloroquine phosphate in patients with renal impairment.

Hepatic Impairment

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Chloroquine phosphate in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Chloroquine phosphate in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

Cyclosporine=

  • After introduction of chloroquine (oral form), a sudden increase in serum cyclosporine level has been reported. Therefore, close monitoring of serum cyclosporine level is recommended and, if necessary, chloroquine should be discontinued.
Geriatric Use
  • Clinical studies of chloroquine phosphate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.

IV Compatibility

There is limited information regarding IV Compatibility of Chloroquine phosphatein the drug label.

Overdosage

Symptoms:=

Treatment:
  • Treatment is symptomatic and must be prompt with immediate evacuation of the stomach by emesis (at home, before transportation to the hospital) or gastric lavage until the stomach is completely emptied. If finely powdered, activated charcoal is introduced by stomach tube, after lavage, and within 30 minutes after ingestion of the antimalarial, it may inhibit further intestinal absorption of the drug. To be effective, the dose of activated charcoal should be at least five times the estimated dose of chloroquine ingested.
  • A patient who survives the acute phase and is asymptomatic should be closely observed for at least six hours. Fluids may be forced, and sufficient ammonium chloride (8 g daily in divided doses for adults) may be administered for a few days to acidify the urine to help promote urinary excretion in cases of both overdosage or sensitivity.

Pharmacology

Chloroquine.png
Chloroquine
Systematic (IUPAC) name
(RS)-N'-(7-chloroquinolin-4-yl)-N,N-diethyl-pentane-1,4-diamine
Identifiers
CAS number 54-05-7
ATC code P01BA01
PubChem 2719
DrugBank DB00608
Chemical data
Formula C18H26ClN3 
Mol. mass 319.872 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability ?
Metabolism Liver
Half life 1–2 months
Excretion ?
Therapeutic considerations
Licence data

US

Pregnancy cat.

?

Legal status

-only(US)

Routes ?

Mechanism of Action

Microbiology=

  • Mechanism of Action: Chloroquine is an antimalarial agent. While the drug can inhibit certain enzymes, its effect is believed to result, at least in part from its interaction with DNA. However, the mechanism of plasmodicidal action of chloroquine is not completely certain.

Structure

  • Chloroquine phosphate, USP is a 4-aminoquinoline compound for oral administration. It is a white crystalline powder; odorless; has a bitter taste, and is discolored slowly on exposure to light. It is freely soluble in water, practically insoluble in alcohol, in chloroform and in ether.
  • Each tablet, for oral administration, contains 250 mg of chloroquine phosphate, USP (equivalent to 150 mg base).
  • Inactive ingredients: colloidal silicon dioxide, corn starch, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, polyethylene glycol 3350, polysorbate 80, povidone, sodium starch glycolate, talc, and titanium dioxide.
  • Chemically, it is 7-chloro-4-((4-(diethylamino)-1-methylbutyl)amino) quinoline phosphate (1:2) and has the following molecular structure:
This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Chloroquine phosphate in the drug label.

Pharmacokinetics

  • Chloroquine is rapidly and almost completely absorbed from the gastrointestinal tract, and only a small proportion of the administered dose is found in the stools. Approximately 55% of the drug in the plasma is bound to nondiffusible plasma constituents. Excretion of chloroquine is quite slow, but is increased by acidification of the urine. Chloroquine is deposited in the tissues in considerable amounts. In animals, from 200 to 700 times the plasma concentration may be found in the liver, spleen, kidney, and lung; leukocytes also concentrate the drug. The brain and spinal cord, in contrast, contain only 10 to 30 times the amount present in plasma.
  • Chloroquine undergoes appreciable degradation in the body. The main metabolite is desethylchloroquine, which accounts for one fourth of the total material appearing in the urine; bisdesethylchloroquine, a carboxylic acid derivative, and other metabolic products as yet uncharacterized are found in small amounts. Slightly more than half of the urinary drug products can be accounted for as unchanged chloroquine.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Chloroquine phosphate in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Chloroquine phosphate in the drug label.

How Supplied

Chloroquine phosphate tablets, USP 250 mg are white to off-white, round, film-coated tablets, debossed with “RF” and “27” on one side and break line on the other side.

NDC 63304-460-03 Bottles of 10

NDC 63304-460-50 Bottles of 50

NDC 63304-460-10 Bottles of 1000

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Protect from light and moisture.

You may report side effects to FDA at 1-800-FDA-1088.

Storage

  • Store at 20 - 25° C (68 - 77° F).

Images

Drug Images

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This pill image is provided by the National Library of Medicine's PillBox.

Package and Label Display Panel

NDC 63304-460-03

CHLOROQUINE PHOSPHATE TABLETS,USP

250 mg

For Use in Malaria and Extraintestinal Amebiasis Only

Rx only

10 Tablets

Chloroquine drug label01.png
This image of the FDA label is provided by the National Library of Medicine.

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Chloroquine phosphate in the drug label.

Precautions with Alcohol

Hepatic Effects
  • Since this drug is known to concentrate in the liver, it should be used with caution in patients with hepatic disease or alcoholism or in conjunction with known hepatotoxic drugs.

Brand Names

  • Aralen Phosphate®

Look-Alike Drug Names

There is limited information regarding Chloroquine Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.


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